Journal article
Pharmacodynamic study using FLT PET/CT in patients with renal cell cancer and other solid malignancies treated with sunitinib malate
Clinical cancer research, Vol.17(24), pp.7634-7644
12/15/2011
DOI: 10.1158/1078-0432.CCR-11-1677
PMCID: PMC3243764
PMID: 22038997
Abstract
To characterize proliferative changes in tumors during the sunitinib malate exposure/withdrawal using 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) positron emission tomography (PET)/computed tomography (CT) imaging.
Patients with advanced solid malignancies and no prior anti-VEGF exposure were enrolled. All patients had metastatic lesions amenable to FLT PET/CT imaging. Sunitinib was initiated at the standard dose of 50 mg p.o. daily either on a 4/2 or 2/1 schedule. FLT PET/CT scans were obtained at baseline, during sunitinib exposure, and after sunitinib withdrawal within cycle #1 of therapy. VEGF levels and sunitinib pharmacokinetic (PK) data were assessed at the same time points.
Sixteen patients (8 patients on 4/2 schedule and 8 patients on 2/1 schedule) completed all three planned FLT PET/CT scans and were evaluable for pharmacodynamic imaging evaluation. During sunitinib withdrawal (change from scans 2 to 3), median FLT PET standardized uptake value (SUV(mean)) increased +15% (range: -14% to 277%; P = 0.047) for the 4/2 schedule and +19% (range: -5.3% to 200%; P = 0.047) for the 2/1 schedule. Sunitinib PK and VEGF ligand levels increased during sunitinib exposure and returned toward baseline during the treatment withdrawal.
The increase of cellular proliferation during sunitinib withdrawal in patients with renal cell carcinoma and other solid malignancies is consistent with a VEGF receptor (VEGFR) tyrosine kinase inhibitor (TKI) withdrawal flare. Univariate and multivariate analysis suggest that plasma VEGF is associated with this flare, with an exploratory analysis implying that patients who experience less clinical benefit have a larger withdrawal flare. This might suggest that patients with a robust compensatory response to VEGFR TKI therapy experience early "angiogenic escape."
Details
- Title: Subtitle
- Pharmacodynamic study using FLT PET/CT in patients with renal cell cancer and other solid malignancies treated with sunitinib malate
- Creators
- Glenn Liu - University of Wisconsin Carbone Cancer CenterRobert Jeraj - University of Wisconsin–MadisonMatt Vanderhoek - University of Wisconsin–MadisonScott Perlman - University of Wisconsin–MadisonJill Kolesar - National Cancer InstituteMichael Harrison - University of Wisconsin Carbone Cancer CenterUrban Simoncic - National Cancer InstituteJens Eickhoff - University of Wisconsin–MadisonLakeesha Carmichael - University of Wisconsin Carbone Cancer CenterBo Chao - University of Wisconsin Carbone Cancer CenterRebecca Marnocha - University of Wisconsin Carbone Cancer CenterPercy Ivy - National Cancer InstituteGeorge Wilding - University of Wisconsin Carbone Cancer Center
- Resource Type
- Journal article
- Publication Details
- Clinical cancer research, Vol.17(24), pp.7634-7644
- DOI
- 10.1158/1078-0432.CCR-11-1677
- PMID
- 22038997
- PMCID
- PMC3243764
- ISSN
- 1078-0432
- eISSN
- 1557-3265
- Grant note
- T32 CA009614-20 / NCI NIH HHS P30 CA014520-37 / NCI NIH HHS T32 CA009206 / NCI NIH HHS T32 CA009614 / NCI NIH HHS P30 CA014520 / NCI NIH HHS P30 CA014520-30 / NCI NIH HHS U01 CA062491 / NCI NIH HHS U01 CA062491-18 / NCI NIH HHS U01 CA062491-19 / NCI NIH HHS K12 CA087718-07 / NCI NIH HHS K12 CA087718 / NCI NIH HHS
- Language
- English
- Date published
- 12/15/2011
- Academic Unit
- Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984695788902771
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